Real-world in vitro activity of newer antibiotics against Enterobacterales and Pseudomonas aeruginosa, including carbapenem-non-susceptible and multidrug-resistant isolates: a multicenter analysis.

Abstract

New antibiotics have been developed to combat antibiotic-resistant Gram-negative pathogens, which are difficult to treat and associated with poor clinical outcomes. We conducted a multicenter evaluation of real-world testing practices and susceptibility to newer antibiotics. Our study included 71 facilities in the BD Insights Research Database (2018-2022) and involved adult patients with a positive culture for Enterobacterales or Pseudomonas aeruginosa and facility-reported antibiotic susceptibility data for cefiderocol (FDC), ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C/T), eravacycline (ERV), imipenem-relabactam (I-R), or meropenem-vaborbactam (MVB). A total of 27,531 susceptibility results were available, including 22,111 (80.3%) Enterobacterales and 5,420 (19.7%) P. aeruginosa. Escherichia coli (11,882 [43.2%]) was the most frequently tested potential pathogen, and CZA (13,567 [49.3%]) and C/T (13,299 [48.3%]) had the greatest numbers of susceptibility results. For the other four antibiotics, susceptibility data were available for fewer than 2% of isolates. Susceptibility comparisons should be considered with caution. Among isolates tested, CZA had the highest susceptibility rates for total Enterobacterales (98.7%) and multidrug-resistant (92.9%) and carbapenem-non-susceptible (85.0%) isolates. For P. aeruginosa, FDC had the highest susceptibility rates for total (95.6%) and carbapenem-non-susceptible (93.3%) isolates. The susceptibility of carbapenem-non-susceptible Enterobacterales to CZA and C/T decreased modestly from 2020 to 2022, but carbapenem-non-susceptible P. aeruginosa susceptibility rates increased. We conclude that Gram-negative pathogens have high real-world susceptibility rates to newer antibiotics but may show important differences across resistance profiles. Newer antibiotics are a valuable option for the management of resistant Enterobacterales and P. aeruginosa. Additional effort may be required to integrate these agents into routine clinical care.IMPORTANCENewer antibiotics against Gram-negative pathogens provide important treatment options, especially for antibiotic-resistant bacteria, but little is known about their use during routine clinical care. To use these agents appropriately, clinicians need to have access to timely susceptibility data. We evaluated 27,531 facility-reported susceptibility results from the BD Insights Research Database to gain a better understanding of real-world testing practices and susceptibility rates for six newer antibiotics. Escherichia coli was the most frequently tested potential pathogen, and ceftazidime-avibactam and ceftolozane-tazobactam had the greatest numbers of susceptibility results. For cefiderocol, eravacycline, imipenem-relabactam, and meropenem-vaborbactam, susceptibility data were available for fewer than 2% of isolates. Susceptibility comparisons should be considered with caution. Ceftazidime-avibactam had the highest susceptibility rates for Enterobacterales while cefiderocol had the highest susceptibility rates for Pseudomonas aeruginosa. New antibiotics have the potential to improve the management of Gram-negative infections, but their use may be hampered by the absence of susceptibility data.